The purpose of this study is to determine whether an optimal dose of [6R] 5,10-methylenetetrahydrofolate (Modufolin) in combination with pemetrexed are effective in pre-operative treatment of patients with resectable rectal cancer.

Feasibility is defined as the ability to receive the total planned dose of pemetrexed (i.e., 1500 mg/m) administered over a period of no more than 9 weeks. Feasibility is measured as absence of the following toxicities:

Correlation between 5,10-methylenetetrahydrofolate and HCy levels in blood [ Time Frame: Samples taken prior before study treatment, during 3 cycles of chemotherapy and after completion of study treatment. Expected average 20 weeks. ] [ Designated as safety issue: No ]

Blood samples are taken before start of study treatment, in conjunction with start of every study drug cycle, and after completed study treatment. HCy measurements performed using HPLC. 5-10-methylenetetrahydrofolate is measured in tissue biopsies (tumor and adjacent mucosa) sampled in conjunction with surgery. The tissue is collected before start of study treatment, during and after completed study treatment. 5,10-methylenetetrahydrofolate levels are measured using LC/MS/MS.

Correlation of folate gene polymorphisms and gene signature profiling with clinical outcome and toxicity profiles. [ Time Frame: Tissue to be collected from tumor and adjacent mucosa before start of study treatment, during and after completed study treatment. Expected average 20 weeks. ] [ Designated as safety issue: No ]

RT-PCR will be used to measure and determine the gene expression levels of the genes FPGS (Folylpolyglutamate synthase) and GGH (Gamma-glutamyl hydrolase). This translational research will be compared with the clinical outcome and toxicity profiles of patients.

Pharmacokinetic parameters of [6R] 5,10-mTHF, 5-formyl-THF, 5-methyl-THF and THF calculated from plasma [ Time Frame: Calculated on Day1 and Day15 after cycle 1 and 3 ] [ Designated as safety issue: No ]

Plasma samples will be collected prior to study treatment, and at 10 minutes, 1, 2 and 4 hours after study treatment

For women: Must be surgically sterile, postmenopausal, or compliant with a medically approved contraceptive regimen during and for 3 months after treatment; must have a negative serum or urine pregnancy test and must not be lactating.

For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 3 months after treatment.

Estimated life expectancy of at least 12 weeks

Signed informed consent

At least 18 years of age

Exclusion Criteria:

Concurrent administration of any other anti-tumor therapy.

Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.

Serious concomitant systemic disorders (e.g., active infection including HIV, cardiac disease) that in the opinion of the investigator would compromise the patient's ability to complete the study.

Have previously completed or withdrawn from this study or any other study investigating pemetrexed.

Are pregnant or breast-feeding.

Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.

History of significant neurological or mental disorder, including seizures or dementia.

Inability to interrupt aspirin or other nonsteroidal anto-inflammatory drugs (NSAIDs)

Presence of clinically relevant third-space fluid collection that cannot be controlled by drainage or other procedures prior to study entry.

Inability or unwillingness to be given 5,10-methylenetetrahydrofolate, vitamin B12 or dexamethasone.

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01397305